Communication between bone marrow mesenchymal stem cells and multiple myeloma cells:Impact on disease progression

Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,and specifically BM mesenchymal stem cells(BM-MSCs),has a key role in the pathophysiology of this disease.Multiple data support the idea that BM-MSCs not only enhance the proliferation and survival of MM cells but are also involved in the resistance of MM cells to certain drugs,aiding the progression of this hematological tumor.The relation of MM cells with the resident BM-MSCs is a two-way interaction.MM modulate the behavior of BM-MSCs altering their expression profile,proliferation rate,osteogenic potential,and expression of senescence markers.In turn,modified BM-MSCs can produce a set of cytokines that would modulate the BM microenvironment to favor disease progression.The interaction between MM cells and BM-MSCs can be mediated by the secretion of a variety of soluble factors and extracellular vesicles carrying microRNAs,long non-coding RNAs or other molecules.However,the communication between these two types of cells could also involve a direct physical interaction through adhesion molecules or tunneling nanotubes.Thus,understanding the way this communication works and developing strategies to interfere in the process,would preclude the expansion of the MM cells and might offer alternative treatments for this incurable disease.

Mesenchymal stem cells secretome:The cornerstone of cell-free regenerative medicine

Mesenchymal stem cells(MSCs)are the most frequently used stem cells in clinical trials due to their easy isolation from various adult tissues,their ability of homing to injury sites and their potential to differentiate into multiple cell types.However,the realization that the beneficial effect of MSCs relies mainly on their paracrine action,rather than on their engraftment in the recipient tissue and subsequent differentiation,has opened the way to cell-free therapeutic strategies in regenerative medicine.All the soluble factors and vesicles secreted by MSCs are commonly known as secretome.MSCs secretome has a key role in cell-to-cell communication and has been proven to be an active mediator of immunemodulation and regeneration both in vitro and in vivo.Moreover,the use of secretome has key advantages over cell-based therapies,such as a lower immunogenicity and easy production,handling and storage.Importantly,MSCs can be modulated to alter their secretome composition to better suit specific therapeutic goals,thus,opening a large number of possibilities.Altogether these advantages now place MSCs secretome at the center of an important number of investigations in different clinical contexts,enabling rapid scientific progress in this field.